Resting‐state functional connectivity predicts the strength of hemispheric lateralization for language processing in temporal lobe epilepsy and normals

In temporal lobe epilepsy (TLE), determining the hemispheric specialization for language before surgery is critical to preserving a patient's cognitive abilities post‐surgery. To date, the major techniques utilized are limited by the capacity of patients to efficiently realize the task. We determined whether resting‐state functional connectivity (rsFC) is a reliable predictor of language hemispheric dominance in right and left TLE patients, relative to controls. We chose three subregions of the inferior frontal cortex (pars orbitalis, pars triangularis, and pars opercularis) as the seed regions. All participants performed both a verb generation task and a resting‐state fMRI procedure. Based on the language task, we computed a laterality index (LI) for the resulting network. This revealed that 96% of the participants were left‐hemisphere dominant, although there remained a large degree of variability in the strength of left lateralization. We tested whether LI correlated with rsFC values emerging from each seed. We revealed a set of regions that was specific to each group. Unique correlations involving the epileptic mesial temporal lobe were revealed for the right and left TLE patients, but not for the controls. Importantly, for both TLE groups, the rsFC emerging from a contralateral seed was the most predictive of LI. Overall, our data depict the broad patterns of rsFC that support strong versus weak left hemisphere language laterality. This project provides the first evidence that rsFC data may potentially be used on its own to verify the strength of hemispheric dominance for language in impaired or pathologic populations. Hum Brain Mapp, 36:288–303, 2015. © 2014 Wiley Periodicals, Inc.     

Intracranial EEG in predicting surgical outcome in frontal lobe epilepsy

Purpose: Surgery in frontal lobe epilepsy (FLE) has a worse prognosis regarding seizure freedom than anterior lobectomy in temporal lobe epilepsy. The current study aimed to assess whether intracranial interictal and ictal EEG findings in addition to clinical and scalp EEG data help to predict outcome in a series of patients who needed invasive recording for FLE surgery. Methods: Patients with FLE who had resective surgery after chronic intracranial EEG recording were included. Outcome predictors were compared in patients with seizure freedom (group 1) and those with recurrent seizures (group 2) at 19–24 months after surgery. Key Findings: Twenty‐five patients (16 female) were included in this study. Mean age of patients at epilepsy surgery was 32.3 ± 15.6 years (range 12–70); mean duration of epilepsy was 16.9 ± 13.4 years (range 1–48). In each outcome group, magnetic resonance imaging revealed frontal lobe lesions in three patients. Fifteen patients (60%) were seizure‐free (Engel class 1), 10 patients (40%) continued to have seizures (two were class II, three were class III, and five were class IV). Lack of seizure freedom was seen more often in patients with epilepsy surgery on the left frontal lobe (group 1, 13%; group 2, 70%; p = 0.009) and on the dominant (27%; 70%; p = 0.049) hemisphere as well as in patients without aura (29%; 80%; p = 0.036), whereas sex, age at surgery, duration of epilepsy, and presence of an MRI lesion in the frontal lobe or extrafrontal structures were not different between groups. Electroencephalographic characteristics associated with lack of seizure freedom included presence of interictal epileptiform discharges in scalp recordings (31%; 90%; p = 0.01). Detailed analysis of intracranial EEG revealed widespread (>2 cm) (13%; 70%; p = 0.01) in contrast to focal seizure onset as well as shorter latency to onset of seizure spread (5.8 ± 6.1 s; 1.5 ± 2.3 s; p = 0.016) and to ictal involvement of brain structures beyond the frontal lobe (23.5 ± 22.4 s; 5.8 ± 5.4 s; p = 0.025) in patients without seizure freedom. The distribution of ictal onset patterns was similar in both groups, and fast rhythmic activity in the beta to gamma range was found in 57% of seizure‐free patients compared to 70% of patients with recurrent seizures. Analysis of the temporal relation between first clinical alterations and EEG seizure onset did not reveal significant differences between both groups of patients. In multivariate analysis, resection in the left hemisphere (odds ratio [OR] 12.197 95% confidence interval [95% CI] 1.33–111.832; p = 0.027) and onset of seizure spread (odds ratio [OR] 0.733, 95% CI 0.549–0.978, p = 0.035) were independent predictors of ongoing seizures. Significance: Widespread epileptogenicity as indicated by rapid onset of spread of ictal activity likely explains lack of seizure freedom following frontal resective surgery. The negative prognostic effect of surgery on the left hemisphere is less clear. Future study is needed to determine if neuronal network properties in this hemisphere point to intrinsic interhemispheric differences or if neurosurgeons are restrained by proximity to eloquent cortex.     

Intraoperative transillumination to determine the extent of frontal sinus in subcranial approach to anterior skull base

We sought to determine the extent of the frontal sinus by intraoperative transillumination through the superomedial orbital wall in a subcranial approach to the anterior skull base. After raising a bicoronal flap, the frontal sinus was transilluminated through the superomedial orbital wall with a fiber-optic light source, delineating the extent of the frontal sinus. The frontal sinus boundary was marked with a marker pen. A frontal sinus anterior wall osteotomy was performed with a sagittal saw, staying within the confines of the frontal sinus marking. A bone flap was removed, and the posterior wall was drilled out. The remaining procedure was performed in a standard fashion. At the end of the procedure, the bone flap was fixed with a titanium plate. A total of 58 patients had undergone craniofacial resection from January 2004 to December 2007. In 13 patients, a subcranial approach was employed using the transillumination technique. Transillumination was successful in delineating the frontal sinus periphery in all 13 patients. Intraoperative transillumination of the frontal sinus through the superomedial orbital wall is a simple and effective method to delineate the frontal sinus periphery in a subcranial approach to the anterior skull base.     

Extratemporal functional connectivity impairments at rest are related to memory performance in mesial temporal epilepsy

Mesial temporal lobe epilepsy (MTLE) is the most frequent form of focal epilepsy. At rest, there is evidence that brain abnormalities in MTLE are not limited to the epileptogenic region, but extend throughout the whole brain. It is also well established that MTLE patients suffer from episodic memory deficits. Thus, we investigated the relation between the functional connectivity seen at rest in fMRI and episodic memory impairments in MTLE. We focused on resting state BOLD activity and evaluated whether functional connectivity (FC) differences emerge from MTL seeds in left and right MTLE groups, compared with healthy controls. Results revealed significant FC reductions in both patient groups, localized in angular gyri, thalami, posterior cingulum and medial frontal cortex. We found that the FC between the left non‐pathologic MTL and the medial frontal cortex was positively correlated with the delayed recall score of a non‐verbal memory test in right MTLE patients, suggesting potential adaptive changes to preserve this memory function. In contrast, we observed a negative correlation between a verbal memory test and the FC between the left pathologic MTL and posterior cingulum in left MTLE patients, suggesting potential functional maladaptative changes in the pathologic hemisphere. Overall, the present study provides some indication that left MTLE may be more impairing than right MTLE patients to normative functional connectivity. Our data also indicates that the pattern of extra‐temporal FC may vary as a function of episodic memory material and each hemisphere's capacity for cognitive reorganization. Hum Brain Mapp 34:2202–2216, 2013. © 2012 Wiley Periodicals, Inc.     

Future trends in spi al cord stimulation

Abstract

Spinal cord stimulation (SCS) has been available for about 30 years, but only in the past five years has it met with widespread acceptance and recognition by the medical community. Traditionally performed by neurosurgeons, SCS is being increasingly utilized by anesthesiologists, orthopedic surgeons and physiatrists. Pain management continues to be the most widespread application of SCS. More sophisticated technology has allowed the implanters to successfully address more complex pain syndromes such as widespread reflex sympathetic dystrophy and the failed back syndrome. Other applications are being developed, combining the ability to stimulate the spinal cord, the nerve roots and the peripheral nerves. Examples include angina pectoris, urinary incontinence and occipital neuralgia. Computer-interactive programming is gaining popularity, especially due to the extreme complexity of the implanted stimulation devices. The ability to stimulate independently multiple channels as well as multiple arrays of electrodes is today a reality. This has increased greatly the efficacy, safety and reliability of the modality. In the future, SCS will undoubtedly move several steps up in the treatment ladder of chronic pain conditions, while new applications will be discovered. The future of neural implantable technologies is bright, with an increasingly important role in the medical management of chronic conditions affecting the nervous system. [Neurol Res 2000; 22: 279-284]     

Age trends in femur stresses from a simulated fall on the hip among men and women: evidence of homeostatic adaptation underlying the decline in hip BMD.

Age trends in proximal femur stresses were evaluated by simulating a fall on the greater trochanter using femur geometry from hip DXA scans of 5334 white men and women in the NHANES III survey. Expansion of femur outer diameter seems to counter net bone loss so that stresses remain similar across age groups, but stresses are higher in older women than in older men. INTRODUCTION: The age decline in hip BMD is caused by both bone loss and expansion of outer diameter that increases the region size over which mass is measured in a DXA scan. Because expansion has an opposing effect on structural strength, it may be a homeostatic adaptation to net bone loss to ensure that load stresses are kept within a narrow range. MATERIALS AND METHODS: Age trends in femur stresses were evaluated with an engineering beam simulation of a fall on the greater trochanter. Hip geometry was extracted from hip DXA scans using the Hip Structure Analysis (HSA) software on 2613 non-Hispanic white men and 2721 women from the third National Health and Nutrition Examination Survey (NHANES III). Using body weight as load, stresses were computed on the inferior-medial and superior-lateral femur neck at its narrowest point and the medial and lateral shaft 2 cm distal to the midpoint of the lesser trochanter. Stresses and the underlying geometries in men and women >50 years oaf age were compared with those 20-49 years of age. RESULTS: Compared with men <50 years of age, stresses in older men were 6% lower on both surfaces of the shaft, 4% lower on the inferior-medial neck, and not different on the superior-lateral neck. In women >50 years of age, stresses on the proximal shaft and inferior-medial neck remained within 3% of young values but were 13% greater on the superior-lateral neck. Neck stresses in young women were lower on the superior-lateral than the inferior-medial neck, but lateral stress increased to the level on the medial surface in older women. Stresses were higher in women than in men, with a greater gender difference in those >50 years of age. CONCLUSIONS: We conclude that femur expansion has a homeostatic effect in men and women that opposes bone loss so that stresses change little with age. Because expansion preserves stresses with progressively less bone mass, the process may reduce structural stability in the femoral neck under fall conditions, especially in the elderly female.     

Long-term survival after chemoradiotherapy for locally advanced squamous cell carcinoma of the esophagus

Seven patients with locally far-advanced, inoperable, squamous cell cancer of the esophagus were given two cycles of concurrent radiation and chemotherapy. Each cycle consisted of 5-fluorouracil 1,000 mg/m2/day given as a continuous intravenous infusion over 96 hours, cisplatin 75 mg/m2 given as an intravenous bolus on day 1, and methotrexate 40 mg/m2 given as an intravenous bolus on days 8 and 15. Three thousand rads of radiation were given in 15 fractions between days 1 and 19. Six patients are evaluable for response. Symptomatic relief was obtained by all six and was complete in 4. Five patients achieved a complete response, and two remain alive and disease free. Five of the six evaluable patients survived for at least 12 months. Aggressive chemoradiotherapy may result in significant survival prolongation and symptomatic palliation in this poor-prognosis subset of patients with esophageal cancer.     

Toremifene prevents prostate cancer in the transgenic adenocarcinoma of mouse prostate model

The chemopreventive efficacy of toremifene, an antiestrogen, was evaluated in the transgenic adenocarcinoma of mouse prostate (TRAMP) model. TRAMP mice were segregated into three groups: (a) the low-dose toremifene group (6.6 mg/kg/day); (b) the high-dose toremifene group (33 mg/kg/day); and (c) the control placebo group. Efficacy of treatment was measured by the absence of palpable tumor. To extend these studies using more sensitive techniques, TRAMP mice were then treated with placebo, flutamide (an antiandrogen; 33 mg/kg/day), or toremifene (10 mg/kg/day). Animals from each treatment group were sacrificed at 7, 10, 15, 20, 25, and 30 weeks of age, and prostate tissues and seminal vesicles were harvested. Tissues from animals (n = 5) in each group were evaluated by wholemount dissections of genitourinary tracts, histology, immunohistochemistry, and Western blot analyses. Blood was pooled per group to measure estradiol and testosterone hormonal levels. Tumors formed at week 17 in the placebo group (n = 10), at week 21 in the high-dose toremifene group (n = 12), and at week 29 in the low-dose toremifene group (n = 12). This represents an increased tumor latency of up to 12 weeks. By 33 weeks, all animals in the placebo group had tumors compared with only 35% of the animals treated with toremifene. Although both flutamide and toremifene decreased tumor incidence compared with the placebo, toremifene was more effective than flutamide. High-grade prostatic intraepithelial neoplasia was observed in animals in the placebo group, but not in animals treated with toremifene. Moreover, toremifene-treated animals had prolonged survival compared with placebo-treated animals. By 33 weeks of age, 100% of the placebo-treated animals had developed palpable tumors and died, whereas 60% of the toremifene-treated animals were tumor free. T antigen levels in the prostate of toremifene-treated animals were similar to those of placebo-treated, age-matched animals. Whereas serum estradiol levels remained unchanged, the total and free testosterone levels were elevated in the toremifene-treated group. Toremifene treatment did not affect androgen receptor levels. Because toremifene prevented prostate cancer in a milieu of elevated blood free testosterone levels with no change in prostate androgen receptor expression, the mechanism of toremifene's chemopreventive activity may be through nonandrogenic pathways, such as estrogen receptor signaling.     

Intrapartum oxytocin use for labor acceleration in rural India

Objective: To examine factors associated with the use of oxytocin for acceleration of labor in women delivered at home in rural India. Method: Quantitative data were collected from 527 women who were delivered at home and qualitative interviews were carried out with 21 mothers and 9 birth attendants. Results: Oxytocin use was associated with higher education and socioeconomic status, primigravidity, and delivery by a traditional birth attendant. Conclusion: Labor acceleration with oxytocin occurs indiscriminately In India. Oxytocin use should be regulated, and training for birth attendants should be provided as well as health education for pregnant women.